The major thrust of this project is to identify the control mechanisms for the development of adriamycin resistance in mammalian cells in culture. It has been found that Adriamycin is a strongly mutagenic agent. Adriamycin-resistant mutants express other phenotypic properties which are not necessarily associated with the resistant state. These include changes in cellular morphology, DNA content, chromosone number, growth properties, and radiation responses. Nuclear transfer techniques, cell hybridization methods, and gene transfer from radiation-killed cells to viable wild type cells will be used in the analysis of Adriamycin resistance. Adriamycin resistance is mediated through the cell membrane and identification of control membranes may have important implications for the regulation of membrane structure and function.